The brain modulates the immune system in an asymmetrical way, as shown by the association between paw preference and immune response in the mice. The purpose of the present work was to study the relationship between plasma tumor necrosis factor-alpha (TNF-alpha), nitric oxide (NO) and nitric oxide synthase (NOS) and brain lateralization. In the study, paw preference test was used to select right-pawed, left-pawed and ambidextrous mice. Mice were classified as the right-pawed if the right paw entry (RPE) score was equal to or greater than 30 (30-50), as the left-pawed if the score was equal to or less than 20 (0-20), and as the ambidextrous if the score was between 21 and 29. One week after the paw preference testing, the animals were injected intraperitoneally with either sterilized 0.9% saline or lipopolysaccharide (LPS) (5 microg/0.5 ml NS) and were killed 2 h later. Plasma was collected from each mouse. The level of plasma TNF-alpha was measured with ELISA kits provided by ENDOGEN. NO and NOS levels of plasma were detected with kits from Juli Biotechnology Company. The results showed that (1) in the normal mice, ambidextrous mice had higher NO levels compared with left-pawed mice (P<0.05). After the injection of LPS, plasma level of TNF-alpha was lower in left-pawed mice compared with those of the right-pawed and ambidextrous mice; plasma level of NO was higher in ambidextrous mice compared with those of the right- (P<0.01) and left-pawed (P<0.05) ones, and there was no significant difference in the plasma levels of NOS among ambidextrous, right- and left-pawed mice. (2) Immune parameters were correlated with the RPE scores. The shape of the curve describing this relation was similar to a parabola. In general, the levels of TNF-alpha, NO, NOS rose along with the increase of RPE if the scores were in the score range of left-pawed mice.After that, they reached a peak if the scores were in the score range of ambidextrous mice. Then they declined along with the increase of RPE if the scores were in the score range of right-pawed mice. In conclusion, plasma levels of TNF-alpha, NO and NOS were associated with brain lateralization, suggesting that the activities of Mo/Mphi were influenced by brain lateralization, and that the immune parameters were correlated with the RPE scores.
Animals ; Brain ; physiology ; Female ; Functional Laterality ; physiology ; Macrophages ; immunology ; Mice ; Mice, Inbred BALB C ; Nitric Oxide ; blood ; Nitric Oxide Synthase ; blood ; Tumor Necrosis Factor-alpha ; blood

Evaluation of the mechanism of anemia in cancer patients might help to select patients for the more efficient use of erythropoietin (EPO, a growth factor for erythroid precursor cells). For this, we investigated whether the production of EPO responds to anemia and the bone marrow responds to EPO appropriately, and whether chronic inflammation is inhibitory to erythropoiesis in anemic cancer children. Serum levels of EPO, soluble transferrin receptor (sTfR), tumor necrosis factor (TNF)-alpha, and erythrocyte sedimentation rate (ESR) in anemic cancer children were measured by enzyme-linked immunosorbent assay and then the correlation coefficients between those parameters and hemoglobin (Hb) were determined. Both in leukemia and in solid tumor patients, there were significant inverse correlations between Hb and EPO (leukemia: tau=-0.547, p<0.0001; solid tumor: tau=-0.591, p<0.0001), and between sTfR and EPO (leukemia: tau=-0.223, p<0.05; solid tumor: tau=-0.401, p<0.05). In contrast, sTfR showed a correlation with Hb in leukemia (tau=0.216, p<0.05) but not in solid tumor patients. sTfR was suppressed in 53% of anemic episodes of leukemia and 78% of those of solid tumor patients. Our results suggest that in cancer children, the EPO production is not defective and chronic inflammation is not inhibitory to erythropoiesis. Rather, the defective erythropoiesis itself is thought to be responsible for the anemia.
Anemia/etiology/*physiopathology ; Blood Sedimentation ; Bone Marrow/physiology ; Child ; Erythropoiesis/*physiology ; Erythropoietin/blood ; Female ; Humans ; Male ; Neoplasms/complications/*physiopathology ; Receptors, Transferrin/blood ; Solubility ; Tumor Necrosis Factor-alpha/metabolism

OBJECTIVETo investigate the variation and the effect of TNF and NO in the process of the creation of protective heat stress model and provide more thoretical basis.

METHODSThe rats were properly treated with heat and then the serum was separated. Radioimmunoassay and nitrate reductase assay were employed to measure the concentration of TNF and NO at different time between 0 h and 24 h after heat stress respectively.

RESULTSCompared with the control, the concentration of TNF increased significantly 2 h, 4 h, 8 h, 12 h after heat stress, of which 2 h, 12 h(P < 0.05), 4 h, 8 h(P < 0.01), but no significant changes 0 h, 24 h after heat stress. The concentration reached the peak 4 h after heat stress[(3.35 +/- 0.20) ng/ml] and increased significantly than 0 h, 2 h, 8 h, 12 h, 24 h after heat stress(P < 0.01, P < 0.05). 24 h after heat stress it recovered to normal standard. Compared with the control, the concentration of NO was higher 2 h, 4 h, 8 h, 12 h, 24 h after heat stress(P < 0.05), but no significance at 0 h. The concentration amounted to peak 8 h after heat stress[(108.21 +/- 27.89) mumol/L] and increased than 0 h, 2 h, 4 h after heat stress(P < 0.01). After 8 h it began to decrease continuously in heat stress group, however it was higher 24 h after heat stress than control.

CONCLUSIONTNF and NO played an important role in the process of the creation of protective heat stress model.

Animals ; Disease Models, Animal ; Heat Stress Disorders ; prevention & control ; Nitric Oxide ; blood ; physiology ; Rats ; Time Factors ; Tumor Necrosis Factor-alpha ; blood ; physiology

OBJECTIVETo probe into effect of electroacupuncture on intestinal permeability in the patient with acute pancreatitis and the mechanism.

METHODSSixty-eight cases of acute pancreatitis were randomly divided into a treatment group and a control group. The control group and the treatment group were treated with anti-infection, inhibiting secretion of pancreas, improving microcirculation and protective agent of gastric mucosa, with electroacupuncture at Zusanli (ST 36), Shangjuxu (ST 37), Gongsun (SP 4), Taichong (LR 3) and Xuanzhong (GB 39) added, twice daily for 3 days, in the treatment group. Their clinical therapeutic effects and changes of endothelin (ET), nitric oxide (NO), tumor necrosis factor (TNF-alpha) and lactulose/mannose ratio (L/M) before and after treatment were compared.

RESULTSThe total effective rate of 86.7% in the treatment group was better than 76.3% in the control group (P < 0.05). After treatment, ET, NO, TNF-alpha contents and L/M all were higher than those before treatment, with those in the treatment group being significantly lower than those in the control group (P < 0.05).

CONCLUSIONElectroacupuncture can significantly decrease permeability of intestinal mucosa in the patient with acute pancreatitis, reduce accumulation of endogenous inflammatory mediators (ET, TNF-alpha) and vascular active substance (NO) in intestinal mucosa, so as to alleviate necrosis of intestinal epithelial cells and protect the barrier of gastro-intestinal mucosa.

Acute Disease ; Adult ; Aged ; Electroacupuncture ; Endothelins ; blood ; Female ; Humans ; Intestinal Mucosa ; metabolism ; Male ; Middle Aged ; Nitric Oxide ; physiology ; Pancreatitis ; metabolism ; therapy ; Permeability ; Tumor Necrosis Factor-alpha ; blood

BACKGROUNDHyperinsulinemic euglycemic clamp is the gold standard to evaluate the insulin sensitivity, but it is too complicated and expensive to use in clinic. We tried to find an alternative indicator to reflect insulin sensitivity. To evaluate the association between the four adipokines, adiponectin, leptin, resistin and tumor necrosis factor-alpha (TNF-alpha) with insulin sensitivity, we used a hyperinsulinemic euglycemic clamp to test insulin sensitivity in Chinese patients with obesity and type 1 or type 2 diabetes mellitus versus controls.

METHODSIn this parallel control study, we tested insulin sensitivity using a hyperinsulinemic euglycemic clamp in different groups, then examined levels of adiponectin, leptin, resistin and TNF-alpha in serum, and the relationship between the different adipokines and glucose disposal rate (M value), as well as insulin sensitivity index (M value/insulin, M/I), which are the "gold standard" indices of insulin sensitivity.

RESULTSThere were significant differences in mean leptin values in the four adipokines from the four different groups (P < 0.001; comparison of the variation between different groups was analyzed by variance analysis). Compared to controls (using multiple comparison two-way Dunnett t test), only the leptin level showed significant differences in the four adipokines from the four different groups at the same time (P < 0.001). The association analysis between the different adipokines and M or M/I values also showed that only leptin negatively correlated with M (r = -0.64, P < 0.001) or M/I values (r = -0.56, P < 0.001); there was no relationship between the other three adipokines and M or M/I values.

CONCLUSIONOnly leptin was associated with M or M/I values. Therefore, leptin might be one of the predictive factors of the degree of insulin resistance and risk of the accompanying disease.

Adipokines ; blood ; Adiponectin ; blood ; Asian Continental Ancestry Group ; Diabetes Mellitus, Type 1 ; blood ; Diabetes Mellitus, Type 2 ; blood ; Glucose Clamp Technique ; Humans ; Insulin Resistance ; physiology ; Leptin ; blood ; Obesity ; blood ; Resistin ; blood ; Tumor Necrosis Factor-alpha ; blood

BACKGROUNDAlthough obstructive sleep apnea (OSA) has been recognized as a major risk factor for cardiovascular complications and its clinical features are well characterized, it is difficult to replicate the OSA hypoxic model in humans. We aimed to establish an experimental rabbit model for chronic OSA and to explore its application to measure blood pressure (BP), myocardial systolic function, and oxidative stress.

METHODSThe rabbit model for OSA was established by repeatedly closing the airway and then reopening it. A tube specially designed with a bag that could be alternately inflated and deflated according to a predetermined time schedule, resulting in recurrent airway occlusions and chronic intermittent hypoxia (CIH) imitating OSA patterns in humans, was used. Twenty-four rabbits were randomly divided into obstruction, sham, and control groups, and their upper airways were alternately closed for 15 s and then reopened for 105 s in a 120-s-long cycle, for 8 h each day over 12 consecutive weeks. Before and after the experiment, the BP of each rabbit was monitored. Levels of interleukin-6 (IL-6) and tumor necrosis factor-&alpha; (TNF-&alpha;) in the serum, superoxide dismutase (SOD) activity, malondialdehyde (MDA) and reactive oxygen species (ROS) contents, as well as Na+-K+-ATPase/Ca2+-ATPase activities in cardiac muscle were examined. In addition, cardiac functional parameters were measured using echocardiography.

RESULTSAfter 3 months, all rabbits in the obstruction group manifested sleepiness performance similar to that observed in OSA patients. Traces of airflow and SpO2showed that this model mimicked the respiratory events involved in OSA, including increased respiratory effort and decreased oxygen saturation. Gradually, the BP rose each month. CIH led to obvious oxidative stress and injured myocardial systolic performance. The serum levels of IL-6 and TNF-&alpha; increased significantly (64.75 ± 9.05 pg/ml vs. 147.00 ± 19.24 pg/ml and 59.38 ± 8.21 pg/ml vs. 264.75 ± 25.54 pg/ml, respectively, both P < 0.001). Compared with the sham and the control groups, myocardial activities of Na+-K+-ATPase/Ca2+-ATPase and SOD in the obstruction group decreased markedly, while ROS and MDA content increased.

CONCLUSIONSThese results show that the rabbit model for OSA simulates the pathophysiological characteristics of OSA in humans, which implies that this animal model is feasible and useful to study the mechanisms involved in the cardiovascular consequences of OSA.

Airway Obstruction ; blood ; pathology ; Animals ; Blood Pressure ; physiology ; Disease Models, Animal ; Female ; Hypoxia ; blood ; pathology ; Interleukin-6 ; blood ; Male ; Malondialdehyde ; blood ; Oxidative Stress ; Rabbits ; Reactive Oxygen Species ; blood ; Sleep Apnea, Obstructive ; blood ; pathology ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the curative effect and histocompatibility of reconstruction of traumatic urethral defect of rabbit using urethral extracellular matrix (ECM).

METHODSUrethral ECM was obtained by excision of the urethra in 20 donor rabbits. In experimental group, 20 rabbits were resected a 1.0 cm-1.5 cm segment of the urethra and artificially made a model of traumatic urethral defect, then reconstructed by the urethral extracellular matrix of the same length. The rabbit immunity response was assessed by lymphocyte transformation test and serum TNF-alpha level. The reconstructed urethral segments were stained with hematoxylin-eosin and Van Gieson stain and observed by histological examination postoperatively. The urethrography, urethroscopy and urodynamic examinations were performed.

RESULTSThere was no significant difference in stimulative index of lymphocyte transformation between ECM group and control group. The serum TNF-alpha levels of ECM group slightly rose, but the increase was not significant as compared with control group. On postoperative day 10, epithelial cell had migrated from each side and small vessels were found in the extracellular matrix. In the 3rd week, several layers of urothelium covered the whole surface of the matrix tube. In the 6th week, the disorganized arrangements of smooth muscle fibers were firstly observed by Van Gieson staining. In the 24th week, the smooth muscle cells increased and the matrix tube appeared fairly similar to normal urethral wall components. The urethroscopy and urodynamic evaluation revealed that the surface of reconstructed urethra was smooth and emiction was unobstructed.

CONCLUSIONThe urethral extracellular matrix might be an ideal and safe biomaterial for the reconstruction of urethral traumatic defect.

Animals ; Extracellular Matrix ; immunology ; physiology ; Female ; Immunohistochemistry ; Lymphocyte Activation ; Rabbits ; Reconstructive Surgical Procedures ; methods ; Tumor Necrosis Factor-alpha ; blood ; Urethra ; immunology ; injuries ; surgery

OBJECTIVETo study the role of tumor necrosis factor-alpha (TNFalpha) on enterocyte apoptosis in the experimental model of fulminant hepatic failure (FHF).

METHODSLiver damage was induced by lipopolysaccharide (LPS)/TNFalpha in D-galactosamine (GalN) sensitized BALB/c mice. Serum TNFalpha levels were determined by enzyme-linked immunosorbent assays (ELISA). The intestinal tissues were studied micro- and ultra-microscopically at 2 h, 6 h, 9 h, 12 h and 24 h time points in mice with fulminant hepatic failure. Enterocyte apoptosis was determined by TUNEL method. The TNFR I expression in the intestinal tissue was tested by immunohistochemistry.

RESULTS(1) Gut mucosa was morphologically normal at every time point in all groups, but typical apoptotic cells could be seen in the experimental groups under the electron microscope. Apoptosis rate of gut mucosal epithelial cells was significantly increased at 6 h (large intestine: 6.47e(-3)+/-2.91e(-4); small intestine: 6.64e(-3)+/-3.78e(-4)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 h (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)), and peaked at 12 h in mice with FHF. (2) TNFalpha induced apoptosis of enterocytes in mice with FHF. Anti-TNFalpha inhibited this effect. (3) The integrated OD (IOD) levels of TNFalpha receptor I protein expressed differently in the intestine of mice with GalN/LPS and GalN/ TNFalpha-induced FHF at 9 h after GalN/LPS and GalN/ TNFalpha administration, in comparison with those of the control groups. IOD level of TNFRI changed significantly at 6 h (large intestine: 2.82e(+4)+/-4.60e(+3); small intestine: 1.14e(+4)+/-2.13e(+3)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)) hours after GalN/LPS and GalN/ TNFa administration. The expression of TNFR1 protein was significantly higher at 9 and 12 h after GalN/LPS and GalN/TNFa administration than other time points. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis.

CONCLUSIONTNFa can induce enterocyte apoptosis in mice with FHF. Anti- TNFalpha IgG can inhibit this role. Excessive TNFRI expression of enterocyte in fulminant hepatic failure can be induced by TNFa, which suggests that TNFalpha can induce apoptosis of enterocyte by up-regulation of TNFRI protein expression.

Animals ; Apoptosis ; physiology ; Enterocytes ; pathology ; Galactosamine ; Lipopolysaccharides ; Liver Failure, Acute ; chemically induced ; pathology ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEGram-negative bacteria-induced multiple organ failure/dysfunction syndrome (MOF/MODS) is one of the leading causes of death through the world. The member of immunoglobulin family programmed death-1 (PD-1) is a negative immune regulator. This study investigated the protective effect of PD-1 as well as the underlying mechanism in LPS-induced endotoxemia.

METHODSTen PD-1(+/+) and ten PD-1 knockout (PD-1(-/-)) mice were injected peritoneally with LPS (10 mg/kg), and the survival was observed within 72 hrs after LPS injection. The other 40 PD-1(+/+) and 40 PD-1(-/-) mice were injected peritoneally with LPS (5 mg/kg). Blood samples were collected before injection and 1.5, 3 and 6 hrs after LPS injection (n=10 each time point). Serum levels of various inflammatory mediators were measured using ELISA.

RESULTSThe survival rate in PD-1(-/-) mice was noticeably lower than that in PD-1(+/+) mice after 10 mg/kg LPS injection. Serum levels of inflammatory mediators TNF-&alpha;, IL-1β, IL-12 and IL-17 in PD-1/mice were higher than those in PD-1(+/+) mice after 5 mg/kg LPS injection.

CONCLUSIONSPD-1 can protect mice from LPS-induced endotoxemia probably through its regulation on inflammatory mediator production.

Animals ; Antigens, Surface ; physiology ; Apoptosis Regulatory Proteins ; physiology ; Endotoxemia ; prevention & control ; Female ; Interleukin-12 ; blood ; Interleukin-17 ; blood ; Interleukin-1beta ; blood ; Lipopolysaccharides ; toxicity ; Mice ; Programmed Cell Death 1 Receptor ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the possible role of inflammation factors in the pathogenesis of impaired glucose tolerance (IGT) with concurrent obstructive sleep apnea/hypopnea syndrome (OSAHS) in pregnant women.

METHODSTwenty-five pregnant women with IGT and concurrent OSAHS and 35 pregnant women with IGT but not OSAHS were monitored for all night polysomnography (PSG), and the apnea hypopnea index (AHI) and the lowest pulse oxygen saturation (LSpO2) were recorded. The body mass index, glycated serum protein (GSP), interleukin-6 (IL-6) and tumor necrosis factor-&alpha; (TNF-&alpha;) were measured in these women.

RESULTSIL-6 and TNF-&alpha; levels increased significantly in women with IGT and OSAHS as compared with those in women without OSAHS. AHI showed significant positive correlations to GSP, IL-6 and TNF-&alpha;, whereas LSpO2 was inversely correlated to GSP, IL-6 and TNF-&alpha;. IL-6 and TNF-&alpha; were significantly correlated to GSP, with correlation coefficients of 0.510 and 0.476, respectively.

CONCLUSIONThe inflammatory factors may play important roles in IGT complicated by OSAHS in pregnant women, and as a potential risk factor, OSAHS may contribute to the occurrence of progression of IGT.

Adult ; Blood Glucose ; metabolism ; Female ; Glucose Tolerance Test ; Humans ; Interleukin-6 ; blood ; Oximetry ; Oxygen ; blood ; Oxygen Consumption ; physiology ; Pregnancy ; Pregnancy Complications ; blood ; Sleep Apnea Syndromes ; blood ; physiopathology ; Tumor Necrosis Factor-alpha ; blood